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Background and Objectives: Low birth weight (LBW) is a major public health problem. LBW is associated with increased neonatal morbidity and mortality. There is no consensus in the literature as to whether maternal copper nutrition is associated with pregnancy outcome or fetal growth. Methods: This case-control study was carried out at Alavi Hospital in Ardabil between August 2008 and August 2009. 56 women who had delivered low-birth- weight infants (

Cognitive impairment is one of the main complications of diabetes and patients with cognitive impairment are considered to be in an intermediate stage of decreased cognition with higher risk of developing dementia and Alzheimer's disease. This study aimed at evaluating serum activity of two esterase enzymes including cholinesterase and paraoxonase 1 (PON 1) in diabetic patients and association with cognitive performance and metabolic parameters. In this crosssectional study, 128 diabetic patients were enrolled. Cognitive performance was evaluated using the Wechsler Adult Intelligence Scale-Revised (WAIS-R). Body mass index, fasting blood glucose, fasting blood insulin, insulin resistance, serum cholinesterase and paraoxonase 1 activity were measured. Prevalence of cognitive impairment was found to be 77% in the study population. Serum cholinesterase activity was found to be higher in diabetic patients with cognitive impairment than the patients with normal cognitive performance (p < 0.04). Further, a negative correlation was found between cognitive performance and cholinesterase activity, albeit statistically non-significant. Alteration in the activity of cholinesterase enzyme was shown to be associated with cognitive impairment in diabetic patients and future studies are required to find the pathophysiological mechanisms of diabetic cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Background: While today different drugs have been used to treat cancer, none of them have proved to be effective. Heavy metal complexes (e.g., platinum and palladium) can be useful in the treatment of cancer. The purpose of this study was to evaluate the effects of newly synthetized palladium complexes on the morphology and clonogenicity of liver cancer cell line (HepG2). Materials and Methods: New palladium complexes were synthesized in the chemistry lab, University of Sistan and Baluchesta. The cytotoxicity and anti-cancer effects of newly synthesized complexes were evaluated using the clonogenic and cell death assay (apoptosis and necrosis) using acridine orange/ ethidium bromide double staining. Results: The results of this study showed that the new complexes had potential concentration-dependent effects on HepG2 cell line. There was a significant difference between the number of colonies formed after treatment with different concentrations of palladium complexes (0.5, 1, 2, 4 and 8 μg/ml) compared to those in the control group (P<0.01). Furthermore, the cells stained with acridine orange/ethidium bromide indicated the occurrence of apoptosis in cancer cells after the treatment with various concentrations of palladium complexes. Conclusion: The results of this study show the anti-cancer effect of palladium complexes on HepG2 cell lines. Also, the palladium complexes can reduce the number of cell colonies and cause cell death by apoptosis. [ABSTRACT FROM AUTHOR]

Introduction: Chemotherapy drugs are used to treat various types of neoplasms. In dong so, such drugs leave many side effects. Furthermore, in recent years, several attempts have been made to develop drugs based on platinum or palladium which have low toxicity and is more sensitive to the drug-resistant diseases. Objective: To evaluate the effects of newly synthetized palladium complexes, as anticancer drugs, on gastric cancer cell line (AGS). Materials & Methods: In this study, gastric cancer cell line (AGS) was purchased from Pasteur Institute, Iran and cultivated in RPMI 1640 and then, the cytotoxic effects of various concentrations of newly synthesized complexes were evaluated by clonogenic assay and acridine orange/ethedium bromide staining. Results: The results showed that the new complexes have different effects in concentration-dependent manner so that complexe l > 0.1 .g /ml, complexe2 > 0.05 .g /ml and complexe 3 > 1 .g /ml lead to cell death by apoptosis and necrosis. Comparison of the number of colonies formed after treatment with concentrations of palladium complexes showed significant differences, compared with controls (P<0.001). Conclusion: In this study, it was demonstrated that the use of low concentrations of palladium complexes of dithiocarbamate derivative increases apoptosis and necrosis, also, reduces the number of cell colonies, thus, it can be considered as an alternative drug for the treatment of gastric cancer. [ABSTRACT FROM AUTHOR]

Background and Objective: Trace elements have been documented to play an important role in the determination of fetal outcome. It has been reported that the pregnant women in developing countries consume diets with a lower amounts of minerals and vitamins. Zinc is an essential trace element and its deficiency can lead to a variety of disorders. Materials and Methods: This case-control study was carried out at Alavi hospital in Ardabil (Iran) from August 2008- August 2009. Fifty six women who had delivered low- birth- weight infants (<2500gr) were taken as the case group and 56 women with infants with normal birth weight (=2500gr) were selected as the control group. Venous blood sample were obtained from the mothers. Serum zinc level was determined by the atomic absorption spectrophotometer method. Results: Mean of birth weight in infants, maternal age, body mass index in mothers and socioeconomic or demographic factors did not differ between case and control groups. Maternal zinc concentration did not differ between Cases and Controls; 55.84 ± 14.40 ìg/dl vs.52.16 ± 8.84 ìg/dl respectively. Conclusion: Results of this study showed that maternal zinc concentration has no impact on neonatal birth weight deliveries. [ABSTRACT FROM AUTHOR]

Detection of abnormalities in brain tissue area in different medical images is inspired by the necessity of high accuracy when dealing with human life. A Variety of diseases occur in brain tissue area such as brain tumour, stroke, infarction, haemorrhage and others. At the present time, the current method that is used for diagnosing those diseases is using a well known digital imaging technique which is Magnetic Resonance Imaging (MRI), though the brain diseases are still difficult to diagnose due to certain circumstances. Thus, Computer Aided System (CAS) is significantly useful due to the fact that it could enhance the results of humans in such domain. It is also important that the false negative cases must be kept at a very low rate. This paper proposes a development of a CAD that implement image processing techniques for segmenting any kind of abnormalities that occur in human brain tissue area. The system is able to determine the patterns and characteristics for each part of particular brain tissue in order to identify any brain abnormalities. The behind idea is that the local textures in the images can reveal the characteristic of abnormalities of the biological structures. Therefore, the system is expected to detect threats in patients and planning for early treatment strategies in the future.

Background: Gastric cancer's (GC) cause is unknown, but its complexity indicates that, in addition to environmental factors, it may have genetic origins. Scientists are studying single-nucleotide polymorphisms (SNPs) in the antisense noncoding RNA in the INK4 locus (ANRIL) gene, which encodes a long noncoding RNA molecule. They found a link between the ANRIL gene product and some polymorphisms and GC, suggesting genetic changes may lead to precancerous conditions. Methods: In a case-control research that included 250 patients with GC and 210 controls who were age- and gender-matched, four SNPs within the ANRIL gene were genotyped. These SNPs were rs1333049, rs496892, rs2383207, and rs2151280. Tetra-primer amplification refractory mutation system-PCR was utilized to carry out the process of genotyping. Results: It was found that the chance of developing GC was connected with three SNPs rs2151280, rs1333049, and rs496892. Nevertheless, rs2383207 did not demonstrate any meaningful connection. In addition, whereas CCTC and TTCC haplotypes were shown to be less common, certain haplotypes that contained these SNPs (TTCG, TCTC, and TTTC) displayed a considerably higher prevalence in the cancer group in comparison to the control group. Conclusion: This study showed novel associations between specific ANRIL gene polymorphisms (SNPs) and the risk of GC. These findings shed light on the potential role of ANRIL SNPs in GC risk and highlight the need for additional research to clarify the underlying functional processes. Understanding these functional processes might lead to developing novel diagnostic or treatment approaches for this cancer.

Background & Aims: Glycation, oxidative stress, and inflammation due to the elevation of transforming growth factor-β1 (TGF-β1) participate in diabetic nephropathy (DN). Thus, we investigated for the first time the effect of crocetin (Crt) on the renal histopathological parameters, TGF-β1 and glycation, oxidative stress, as well as inflammatory markers in the DN rat model., Methods: Forty male Wistar rats were randomly divided into 4 equal groups: normal (N), N + Crt, DN, and DN + Crt. DN was induced in rats with a combination of nephrectomy and streptozotocin. Treated groups received 100 mg/kg of Crt via intraperitoneal injection monthly for 3 months. Different glycation (glycated albumin, glycated LDL, Methylglyoxal, and pentosidine), oxidative stress (advanced oxidation protein products, malondialdehyde, glutathione, and paraoxonase-I (PON-1)), and inflammatory markers (tumor necrosis factor-α, myeloperoxidase, and TGF-β1), blood glucose, insulin, lipid profile, creatinine in the serum, and proteinuria, as well as the glyoxalase-1 (GLO-1) activity, was determined., Results: Crt decreased renal biochemical (Cre and PU) and histopathological (glomerulosclerosis) renal dysfunction parameters, diverse glycation, oxidative stress, and inflammatory markers in the DN rats. Furthermore, the treatment corrected glycemia, insulin resistance, and dyslipidemia as well as induced the activities of GLO-1 and PON-1. Over and above, the treatment decreased TGF-β1 in their serum (p > 0.001)., Conclusions: Crocetin improved DN owing to an advantageous effect on metabolic profile. Further, the treatment with a reducing effect on TGF-β1, oxidative stress, glycation, and inflammation markers along with an increase in Glo-1 activity showed multiple protective effects on kidney tissue., Competing Interests: Declaration of competing interest There is no conflict interest., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Oral mucositis is one of the most serious complications due to chemotherapy and radiotherapy in head and neck cancer treatment. Oral mucositis causes a wide range of clinical signs and symptoms, such as ulcers, pain, and dysphagia. Additionally, because of speech limitations, patients' self-esteem will decrease, ultimately causing reduced quality of life. The primary objective of this study was to investigate the role of diet in the onset and progress of mucositis induced by chemotherapy and radiation therapy in patients with cancers., Methods: In this study, 121 patients with a mean age of 51.43 ± 13.08 years were selected randomly and referred to the cancer institute, where they underwent their first phase of chemotherapy. In this step, patients were examined and their severity of oral mucositis was graded according to the World Health Organization criteria. They completed a 3-day allergen food recall and dietary recommendations were met. After completing the forms, four questionnaires were filled out for each patient, the patient's nutrition was analyzed using the N4 software, and the amount of macro- and micronutrients was measured., Results: Micronutrients such as aspartic acid, glycine, serine, proline, alanine, arginine, glutamic acid, and vitamin B12 and macronutrients such as rose water, sausage, beverages, coffee, and lamb meat were examined, and a significant difference was observed between groups (grade 1 and 2 mucositis) ( p  < 0.005). In patients with grade 2 mucositis, a lower level of vitamin B12 was reported ( p  < 0.005). There is a negative correlation between amounts of macro- and micronutrients and grades of oral mucositis., Conclusion: It can be concluded that diet plays a considerable role in the severity of oral mucositis caused by cancer treatment., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

The aim of the current study is to determine the protective and therapeutic effects of linalool against carbon tetrachloride (CCl 4 )-induced hepatoxicity and nephrotoxicity. Six-week-old male Wistar rats were divided into five groups: Control group (a regular diet); CCl 4 group (1 ml/kg dissolved in olive oil, intraperitoneally at 14th day); pretreatment group (25 mg/kg linalool daily + CCl 4 14thday); post-treatment group (25 mg/kg linalool 2, 6, 24, and 48 h after the injection of CCl 4 at 14 th day); and linalool group (25 mg/kg linalool daily, orally). All animals were sacrificed, tissue and blood samples were collected to analysis. Administration of CCl 4 resulted in a marked increase in hepatic (aspartate aminotransferase, alanine transaminase, and alkaline phosphatase) and renal (blood urea nitrogen and creatinine) markers. Also, CCl 4 resulted in pathological damages, a significant increase in the concentration of malondialdehyde , tumor necrosis factor-alpha, and Interleukin 6 , expression of nuclear factor kappa-light-chain-enhancer of activated B cells and a significant decrease in the levels of serum total protein, serum albumin, and antioxidants. However, in pretreatment and post treatment groups, linalool significantly inhibited CCl4- induced hepatic and nephric damages. These results demonstrate that linalool has protective and therapeutic effects in an in vitro model of CCL 4 -induced hepatic and nephric damage, proposing linalool as a potential therapeutic agent against chemical and drug induced hepatotoxicity and nephrotoxicity.

Objectives: Ficus carica (fig) and Olea europaea (olive) are valuable nutritional plants that are widely used in diet and traditional medicine. Different parts of the plants such as fruit and leaves contain beneficial compounds with diverse pharmacological properties, among which anti-inflammatory activities are remarkable. The purpose of this review is to discuss the anti-inflammatory effects of F. carica and O. europaea with emphasis on their impact on pivotal pro-inflammatory cytokines including IL-1, IL-6, and TNF-α., Materials and Methods: To prepare the present review, the sites utilized included Scopus, PubMed, Science Direct, and Google Scholar and studied relevant articles from 2000 until 2021., Results: As a result, we observed that most of the compounds in fig and olive including polyphenols, flavonoids, etc., exert their anti-inflammatory effects through inhibiting or decreasing pro-inflammatory cytokines. Moreover, some natural antioxidants are common between these two plants., Conclusion: We suggest that consuming figs and olives simultaneously or alone can be useful in the prevention or treatment of inflammatory diseases., Competing Interests: None.

Sexual dysfunction of men is one of the most serious problems in human society. This study aimed to evaluate the protective effect of cinnamon and ginger extract on testicular damages induced by carbon tetrachloride (CCl4). Thirty-six male Wistar rats were randomly divided into 6 groups (n = 6): 1. Normal control; 2. Carbon tetrachloride (CCl4); 3. CCl4 + Cinnamon; 4. CCl4 + Ginger; 5. CCl4 + Cinnamon and Ginger; and 6. Cinnamon + Ginger. CCl4 (1 ml/kg) was injected intraperitoneally on the 14th day, and cinnamon (50 mg/kg, orally) and ginger (250 mg/kg, orally) were administered daily for 14 days. Fifty hours after the CCl4 injection, the testicles and epididymis were separated and examined as to histological alterations and oxidative stress markers. CCl4 significantly increased malondialdehyde level and decreased total antioxidant capacity when compared to the normal control group (p < .05). In addition, degenerative alterations in the testicular and epididymal tissue were observed in CCl4 group. The pre-treatment with ginger and cinnamon extract significantly improved these parameters when compared to the CCl4 group (p < .05). The results of this study indicated that co-treatment of ginger and cinnamon reduces the damages induced by CCl4 in testicular tissue by increasing antioxidant capacity and reducing lipid peroxidation., (© 2020 Blackwell Verlag GmbH.)

2,4-Dicholorophenoxy acetic acid (2,4-D) is a worldwide used hormone herbicide. Human dental pulp stem cells (hDPSCs) as a potential source of mesenchymal stem cells provide a confident model system for the assessments of chemicals in vitro. The main objective of this study was to examine the biological effects and damages attributed to 2,4-D on hDPSCs. hDPSCs were isolated from third molar pulp tissues and their mesenchymal identity were evaluated. Then, hDPSCs were treated with increasing concentrations of 2,4-D (0.1 μM-10 mM). Cell viability assay and cumulative cell counting were carried out to address 2,4-D effects on biological parameters of hDPSCs. Cell cycle distribution, ROS level and ALP activity were measured before and after treatment. AO/EB staining and caspase 3/7 activity were investigated to detect the possible mechanisms of cell death. Flow-cytometric immunophenotyping and differentiation data confirmed the mesenchymal identity of cultivated hDPSCs. 2,4-D treatment caused a hormetic response in the viability and growth rate of hDPSCs. G0/G1 cell cycle arrest, enhanced ROS level, and reduced ALP activity were detected in hDPSCs treated with EC50 dose of 2,4-D. AO/EB staining showed a higher percentage of alive cells in lower concentrations of the herbicide. The increment in 2,4-D dose and the number of early and late apoptotic cells were increased. DAPI staining and caspase 3/7 assay validated the induction of apoptosis. 2,4-D concentrations up to 100 μM did not affect hDPSCs viability and proliferation. The intense cellular oxidative stress and apoptosis were observed at higher concentration.

Objective: To investigate the efficacy of L-carnitine (LC) and conjugated linoleic acid (CLA) supplements on haemoglobin levels and inflammatory markers in chronic kidney disease (CKD) patients with different haptoglobin (HP) genotypes., Methods: This clinical trial study was conducted at Imam Khomeini Hospital, Ardabil, and Labbafinejad Hospital, Tehran, Iran, from March 2014 to March 2015, and comprised male patients with CKD and anaemia. Anthropometric factors were recorded and demographic data was collected using general questionnaires. LC (1 g/day) and CLA (2.4 g/day) supplements were given to the patients for a month. Blood samples were taken to measure haematological and inflammatory markers at the beginning and end of the study. Haptoglobin genotypes were determined using polymerase chain reaction (PCR). SPSS 21 was used for data analysis., Results: Among the 40 patients in the study, HP2-2 genotype was the most prevalent genotype (62.5%). The level of haemoglobin was significantly increased in the patients at the end of the study (p< 0.05). No significant changes were found in the weight, body mass index and serum levels of Interleukin-6, high-sensitivity C-reactive protein, ferritin, total iron-binding capacity and iron (p>0.05 each)., Conclusions: Regular diet supplementation with LC plus CLA can improve haemoglobin levels in CKD patients with anaemia.

Objective: To evaluate the effect of probiotic yoghurt consumption on oxidative stress and inflammatory factors in young females after exhaustive exercise., Methods: TThis study included 27 healthy participants with an age range of 18-25. For two weeks, 450 grams of probiotic yoghurt and 450 grams of ordinary yoghurt were given to the supplement and control groups, respectively. Fasting blood samples were taken at baseline and at the end of study. At the end of the intervention, the participants were given one exhaustive exercise and then fasting blood samples were taken to test for blood antioxidant enzymes, inflammatory markers, and oxidative markers. Data were analyzed using descriptive statistics as well as paired and independent samples t-test., Results: In supplement group, the glutathione peroxidise (GPX) blood levels and serum levels of total antioxidant capacity (TAC) significantly increased at the end of two weeks of intervention (p<0.05). After intense physical activity, the blood levels of superoxide dismutase (SOD), GPX and serum levels of TAC significantly increased, whereas the serum level of tumour necrosis factor alpha (TNF-?), matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), and malondialdehyde (MDA) significantly decreased in the supplement group compared to the control group (p<0.05). Besides, there were no significant changes in other biochemical factors., Conclusions: Regular probiotic yoghurt consumption significantly modulated MMP2, MMP9 and some inflammatory factors, and thus guarded against exhaustive exercise-inducing oxidative injury in young healthy females.

Background: All-trans retinoic acid (ATRA) is a differentiating agent that inhibits cancer cell growth during the cell cycle. However, despite its potent antitumor properties, some melanoma cells are resistant to ATRA therapy., Purpose: Here, we hypothesized that allicin can sensitize malignant melanoma cells to ATRA treatment. To clarify this mechanism, we determined the sensitivity to ATRA, allicin and allicin/ATRA in CD44 + and CD117 + melanoma cell subpopulations., Methods: The CD44 + and CD117 + cells were sorted from A375 melanoma cell line using the magnetic-activated cell sorting (MACS). The potential anticancer effects of ATRA, allicin and allicin/ATRA were examined using cell proliferation MTT assay. In addition, flow cytometry was used to detect cell cycle arrest. The efficacy of the treatments in controlling cancer cell proliferation was assessed by quantitative realtime polymerase chain reaction (RT-PCR)., Results: Here, we demonstrated that CD44 + melanoma cells were more resistant to allicin and ATRA than CD117 + cells. Importantly, we observed that allicin sensitized melanoma cell to ATRA-induced cell death. The combination treatment with allicin and ATRA significantly reduced the IC 50 value obtained for ATRA alone in CD44 + melanoma cells. In CD44 + cells, the IC 50 value of ATRA was 37.43 ± 0.54, while the IC 50 value of allicin/ATRA treatment was 17.53 ± 0.2 µM. Allicin treatment resulted in significant increases in the percentage of cells at the G2/M and G0/G1 phases in the CD44 + and CD117 + cells, respectively. The combination treatment caused the inhibition of CD44 + and CD117 + melanoma cells at the S phases compared to ATRA alone. Allicin, ATRA, and allicin/ATRA increased the expression of cyclin D1 mRNA in both CD44 + and CD117 + cells. Allicin combination with ATRA increased the mRNA level of RARβ in CD117 + cells. Furthermore, allicin alone caused a remarkable reduction of MMP-9 mRNA expression in both CD44 + and CD117 + cells. In contrast, ATRA and the combination treatment significantly increased MMP-9 gene expression in CD44 + cells., Conclusion: Overall, our results indicate that allicin reinforces the ATRA-mediated inhibitory effects on CD44 + and CD117 + melanoma cells and may provide a new approach for the treatment of malignant melanoma., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Immunotherapy is one promising therapeutic strategy against glioma, an aggressive form of brain cancer. Previous studies have demonstrated that multiple tumor antigens exist and can be used to induce tumor specific T cell responses. Furthermore, recently it was shown that TLR4-primed mesenchymal stem cells (MSCs), also known as MSC1, mostly elaborate pro-inflammatory mediators. Compared to MSCs, MSC-derived microvesicles (MVs) have advantageous properties that present them as stable, long lasting effectors with no risk of immune rejection. Therefore, peripheral blood monocyte derived dendritic cells (MoDCs) have been used to load tumor antigens and stimulate T cell mediated responses in the presence of MSC1-derived MVs in vitro. Methods: The B92 tumor cell line was heated to 43°C for 90 min prior to preparation of tumor cell lysates. MVs were purified by differential ultracentrifugation after isolation, stimulation of proliferation and treatment of MSCs. Autologous T cells isolated from non-adherent cells were harvested during the procedure to generate MoDCs and then incubated with heat stressed tumor cell lysate pulsed DCs in the presence of MSC1-derived MVs. T cells were then co-cultured with tumor cells in 96-well plates at a final volume of 200 μl CM at an effector: target ratio of 100:1 to determine their specific cytotoxic activity. Results: Flow cytometric analysis, T cell mediated cytotoxicity showed that heat stressed tumor antigen pulsed MoDCs and MSC1-derived MVs primed T cells elicited non-significantly enhanced cytotoxic activity toward B92 tumor cells (P≥0.05). Conclusion: These findings may offer new insights into tumor antigen presenting technology involving dendritic cells and MSC1-derived MVs. Further exploration of the potential of such nanoscale particles in immunotherapy and in novel cancer vaccine settings appears warranted., (Creative Commons Attribution License)

Objective: Studies have demonstrated that carbon tetrachloride (CCl 4 ) increases the generation of reactive oxygen species (ROS) in many tissues including the kidney, heart, lung, brain, and liver. The major aim of the present study was to evaluate the protective activity of Tanacetum parthenium extract (TPE) in renal tissues of CCl 4 -intoxicated rats., Materials and Methods: Animals were divided into seven groups of six rats. Group 1 was the control group that was not treated with CCl 4 . The rats in the other groups were intraperitoneally injected with CCl 4 (1.5 ml/kg, 1:1 in olive oil) on day 14. Rats in the groups bTPE40, bTPE80, and bTPE120 were gavaged with 40, 80, and 120 mg/kg of TPE, respectively for 14 constitutive days on a daily basis, before CCl 4 administration. Rats in groups aTPE80 and aTPE120 were gavaged with 80 and 120 mg/kg of TPE, respectively, 2, 6, 24 and 48 hr after receiving CCl 4 . Blood samples were collected at the end of the 16 th day through an intracardiac puncture and then serums were separated., Results: CCl 4 increased urea, creatinine, uric acid and creatinine: albumin (C/A) ratio level in serum and decreased total antioxidant and antioxidant enzymes (SOD and GPx) when compared to the control group (p<0.001). But administration of TPE to rats either before or after exposure to CCl 4 , attenuated these changes when compared with CCl 4 control group (p<0.05 - p<0.001)., Conclusion: TPE had potent nephroprotective effects against oxygen free radicals produced through CCl 4 metabolism., Competing Interests: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

2,4-dicholorophenoxy acetic acid (2,4-D) is a worldwide-known hormone herbicide. However, there are increasing concerns about its exposure and risks of developing pathological conditions for the peripheral nervous system. The aim of this study was to investigate the mechanism(s) involved in the toxicity of 2,4-D on peripheral nerve's cellular components. The epi/perineural and Schwann cells and a total of three cell lines were treated with 2,4-D. The viability of cells at different doses of 2,4-D was measured by MTT assay. The cell cycle analyses, cumulative cell counting, fluorescent staining, antioxidant and caspase enzymes activity were examined on epi/perineural and Schwann cells. The epi/perineural cells were assessed as having biological macromolecular changes. Some tight junction-related genes and proteins were also tested on explants of 2,4-D treated epi/perineural tissue. The viability of 2,4-D treated cells was reduced in a dose-dependent manner. Reduced growth rate and G1 cell cycle arrest were verified in 2,4-D treated epi/perineural and Schwann cells. The use of staining methods (acridine orange/ethidium bromide and DAPI) and caspase 3/7 activity assay along with malondialdehyde, glutathione peroxidase, and superoxide dismutase activity assays indicated the apoptotic and oxidant effects of 2,4-D on epi/perineural and Schwann cells. Data obtained from FTIR revealed changes in epi/perineural proteins and cell membrane lipids. Additionally, claudin-1, occludin, and ZO-1 gene/protein expression profiles were significantly reduced in 2,4-D-treated epi/perineural pieces. Our data indicated that oxidative stress, apoptosis of epi/perineural and Schwann cell and impaired blood-nerve barrier may have contributed to nerve damage following 2,4-D exposure.

Background. The aim of this study was to evaluate the effectiveness of different concentrations of sodium hypochlorite (NaOCl) solution in reducing bacterial growth in Enterococcus faecalis biofilms in root canals. Methods. The root canals of maxillary central incisors of 104 subjects underwent chemomechanical debridement. In order to remove the smear layer, 5.25% sodium hypochlorite solution was used for 3 minutes in the root canals. Then, the samples were immersed in 1 mL of 17% EDTA for 3 minutes. Finally, the root canals were irrigated with phosphate-buffered saline (PBS) solution. After removing the smear layer, the samples were sterilized. Then E. faecalis biofilms formed within the root canals at 4-, 6-, and 10-week intervals were evaluated. Each group was divided into 4 subgroups in terms of the antibacterial treatment: group 1: 1% NaOCl solution; group 2: 2.5% NaOCl solution; group 3: 5.25% NaOCl solution; and group 4: PBS solution. After preparation of root canal filings, the counts of live bacteria were calculated through the classic method of counting, i.e. colony forming units (CFU), followed by the analysis of data. Results. In groups 2 and 3, there was no bacterial growth due to complete removal of E. faecalis biofilms (P<0001), while the bacterial counts in group 1 at 4-, 6- and 10-week intervals decreased compared to the control group. Conclusion. The bacterial cells in mature and old biofilms have higher resistance to 1% NaOCl solution compared to the young biofilms. However, the 2.5% and 5.25% NaOCl solutions caused complete inhibition of the growth of E. faecalis biofilm in all the stages of development.

The purpose of this study was to investigate the effects of Tanacetum Parthenium Extract (TPE) on Lipid peroxidation, antioxidant enzymes, biochemical factors, and liver enzymes in the rats damaged by Carbon Tetrachloride (CCl4). 54 male Wistar rats were divided into 9 groups each consisting of 6 rats. Two of the groups were control groups (normal and damage control groups), 4 of them were exposure groups which were respectively administered with 40, 80, and 120 mg/kg of TPE and silymarin for 14 days before being damaged by CCl4, and the other 3 groups were post-treatment groups which received 80 and 120 mg/kg of TPE and silymarin 2, 6, 24, and 48 h after being injected with CCl4. At the end of the study, biochemical factors, serum liver enzymes, malondialdehyde level, antioxidant enzymes, and liver morphology were assayed. Pre- and post-treatment with TPE could significantly decrease ALT, AST, ALP, TG, LDL, TC, and glucose levels and increase HDL, and albumin levels and catalase, SOD, and GPx activities compared to the CCl4-damaged control group. The results of this study are indicative of the antioxidant activity of TPE, its potential hepatoprotective effects, and its probable therapeutic properties for laboratory animals damaged by CCl4.

Protein stability is a subject of interest by many researchers. One of the common methods to increase the protein stability is using the osmolytes. Many studies and theories analyzed and explained osmolytic effect by equilibrium thermodynamic while most proteins undergo an irreversible denaturation. In current study we investigated the effect of sucrose as an osmolyte on the thermal denaturation of pea seedlings amine oxidase by the enzyme activity, fluorescence spectroscopy, circular dichroism, and differential scanning calorimetry. All experiments are in agreement that pea seedlings amine oxidase denaturation is controlled kinetically and its kinetic stability is increased in presence of sucrose. Differential scanning calorimetry experiments at different scanning rates showed that pea seedlings amine oxidase unfolding obeys two-state irreversible model. Fitting the differential scanning calorimetry data to two-state irreversible model showed that unfolding enthalpy and T * , temperature at which rate constant equals unit per minute, are increased while activation energy is not affected by increase in sucrose concentration. We concluded that osmolytes decrease the molecular oscillation of irreversible proteins which leads to decline in unfolding rate constant.

Objective: To explore the efficacy of conjugated linoleic acid supplementation on some inflammatory factors in young healthy males during exhaustive exercise., Methods: The randomised double-blind controlled study was conducted at Ardabil University of Medical Sciences, Iran, from December 2012 to March2013, and comprised healthy male athletes 18-24 years of age. The subjects were randomly distributed into control and intervention groups. About 5.6 g/day conjugated linoleic acid supplement and oral paraffin (placebo) were given to intervention and control groups respectively daily for two weeks. Fasting blood samples were taken at baseline and at the end of the two weeks of intervention. The subjects underwent exhaustive exercise and then fasting blood samples were taken. Serum levels of tumour necrosis factor alpha, interleukin-6, high-sensitivity C-reactive protein, matrix metalloproteinases-2 and 9 were measured., Results: There were 23 subjects in the study, with 13(56.5%) in the supplemented group and 10(43.4%) in the control group. Serum levels of matrix metalloproteinases-2 and tumour necrosis factor alpha were significantly decreased in the supplemented group (p<0.05). After exhaustive exercise, serum levels of matrix metalloproteinases-2, high-sensitivity C-reactive protein and tumour necrosis factor alpha significantly decreased in the supplemented group compared to the control group(p<0.05)., Conclusions: Two-week administration of conjugated linoleic acid reduced the inflammatory factors following exhaustive exercise in young healthy males.

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation. Here, we report the identification and separation of CD44(+) cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44(±) cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry. Low concentration of ATRA (1μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44(±) cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1. We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Background: Methotrexate (MTX) is an antimetabolite broadly used in treatment of cancer and autoimmune diseases. MTX-induced hepatotoxicity limits its application. We investigated hepatoprotective effects of turmeric in MTX-induced liver toxicity., Methods: All experiments were performed on male Wistar albino rats that were randomly divided into six groups. Group one received saline orally for 30 days (control group), groups two and three received turmeric extract (100, 200 mg/kg respectively) orally for 30 days, group four received single dose, of MTX IP at day 30, groups five and six received turmeric extract 100 and 200 mg/kg orally respectively for 30 days and single dose of methoterxate IP (20 mg/kg) at day 30. Four days after MTX injection animals were sacrificed and evaluated. Blood ALT and AST (indicators of hepatocyte injury), ALP and bilirubin (markers of biliary function), albumin (reflect liver synthetic function) as well as the plasma TAS concentration (antioxidant defenses) were determined. The cellular antioxidant defense activities were examined in liver tissue samples using SOD, CAT, and GSH-Px for the oxidative stress, and MDA for lipid peroxidation. In addition, liver damage was evaluated histopathologically., Results: MTX significantly induced liver damage (P<0.05) and decreased its antioxidant capacity, while turmeric was hepatoprotective. Liver tissue microscopic evaluation showed that MTX treatment induced severe centrilobular and periportal degeneration, hyperemia of portal vein, increased artery inflammatory cells infiltration and necrosis, while all of histopathological changes were attenuated by turmeric (200 mg/kg)., Conclusion: Turmeric extract can successfully attenuate MTX-hepatotoxicity. The effect is partly mediated through extract's antinflammatory activity.

Aim: The aim of this study was to investigate Punica granatum juice effects on oxidative stress in young healthy males during severe physical activity., Methods: Our subjects were selected from healthy males at 18 - 24 years. They were enrolled and randomly distributed into control and supplemented groups. 240 ml of Punica granatum juice and tap water were given to supplement and control groups daily for two weeks, respectively. Fasting blood samples were taken at the starting and the end of two weeks of intervention. Subjects were given once severe physical activity and then fasting blood samples were taken. Fasting blood samples were used for testing of oxidative and antioxidative factors. Data were analyzed using descriptive statistical tests, paired samples t-test, and independent samples t-test., Results: The levels of arylesterase, superoxide dismutase, glutathione peroxidase and total antioxidant capacity after severe physical activity in supplement group were significantly increased (p<0.05), while the content of malondialdehyde showed a significantly decrease in comparison to control group (p<0.05)., Conclusion: Our findings indicate that regular intake of Punica granatum juice significantly modulates oxidative stress and thus protects against severe physical activity oxidative injury in young healthy males.

Purpose: It is estimated that one third of the world's population were infected with M. tuberculosis, but only 10% of them have developed in to disease form. This subject refers to differences in host immune system activity against the tuberculosis. Vitamin D and its receptor (VDR) are important factors in the host innate immune system against the tuberculosis. In the present study VDR gene polymorphisms and its relationship with plasma vitamin D levels in susceptibility to tuberculosis have been investigated., Methods: The subjects were 84 patients with tuberculosis and 90 healthy controls. Vitamin D levels were measured in all study participants. DNA was isolated from the blood leukocytes of all groups and amplified by polymerase chain reaction (PCR). Then restriction fragment length polymorphism (RFLP) was performed on each PCR products to study the VDR gene polymorphisms. The statistical analyses were conducted using SPSS., Results: There was no statistically significant relationship between polymorphisms of FokI, BsmI, ApaI and TaqI in VDR gene and susceptibility to tuberculosis. Vitamin D deficiency and susceptibility to tuberculosis were closely related (95% CI -0.08 - 4.7, P = 0.059). Also the relationship between plasma vitamin D levels and frequency of FokI-ff gene polymorphism was significant in all study participants (P = 0.045)., Conclusion: When the genotype frequencies of VDR gene polymorphisms were analyzed with respect to plasma vitamin D levels, a significant association was seen. As an enhancement in plasma vitamin D levels in individuals (with FokI-ff genotype and low levels of vitamin D) may protect them against active tuberculosis.

Objectives: To evaluate the efficacy of pomegranate juice supplementation on matrix metalloproteinases2 and 9 serum levels and improving antioxidant function in young healthy males during exhaustive exercise., Methods: The study was conducted at Ardabil University of Medical Sciences, Iran, in 2010-11 and comprised 28 healthy subjects in 18-24 age bracket. They were randomly divided into control and supplemented groups. One cup of pomegranate juice and one cup of tap water were given to supplemented and control groups daily for two weeks respectively. Fasting blood samples were taken at baseline and at the end of two weeks of intervention. The subjects were given one exhaustive exercise and then fasting blood samples were taken for testing blood glutathione peroxidase and superoxide dismutase and serum levels of high sensitivity C-reactive protein, zinc, ceruloplasmin, matrix metalloproteinases 2 and 9, malondialdehyde and total antioxidant capacity. Data was analysed using descriptive statistical tests, paired and independent sample t-test., Results: The blood levels of glutathione peroxidase and superoxide dismutase and serum levels of total antioxidant capacity after exhaustive exercise in the supplemented group were significantly increased (p < 0.05), while the content of matrix metalloproteinases 2 and 9, ceruloplasmin and malondialdehyde showed a significant decrease in comparison to the control group (p < 0.05). Besides, there were no significant changes in other biochemical factors., Conclusion: Regular intake of pomegranate juice significantly modulates matrix metalloproteinases 2 and 9and serum levels of some inflammatory factors and thus protects against exhaustive exercise-induced oxidative injury in young healthy males.

As a part of a drug development program to discover novel therapeutic and more effective palladium (Pd) based anticancer drugs, a series of water-soluble Pd complexes have been synthesized by interaction between [Pd (phen)(H2O)2(NO3)2] and alkylenebisdithiocarbamate(al-bis-dtc) disodium salts. This study was undertaken to examine the possible cytotoxic effect of three novel complexes (0.125-64 µg/mL) on human gastric carcinoma (AGS), esophageal squamous cell carcinoma (Kyse-30), and hepatocellular carcinoma (HepG2) cell lines. The cytotoxicity was examined using cell proliferation and acridine orange/ethidium bromide (AO/EB) assay. In order to examine the effects of new Pd(II) complexes on cell cycle status, we performed cell cycle analysis. The complexes were found to have completely lethal effects on the cell lines, and the half maximal inhibitory concentration (IC50) values obtained for the cell lines were much lower in comparison with cisplatin. We demonstrated that the three new Pd(II) complexes are able to induce G2/M phase arrest in AGS and HepG2; in addition, the Pd(II) complexes caused an S phase arrest in Kyse-30 cell line. Our results indicate that newly synthesized Pd(II) complexes may provide a novel class of chemopreventive compounds for anticancer therapy.

Aim: The most important side effect of methotrexate (MTX) is mucositis. The purpose of this study was to evaluate the effect of turmeric extract on intestinal damage and oxidative stress in rats receiving methotrexate., Methods: Experiments were performed on male Wistar albino rats divided into six groups. First group received normal saline orally, the second group received turmeric extract (100 mg·kg(-1)) orally for 30 days, the third group received turmeric extract (200 mg·kg(-1)) orally for 30 days, the fourth group received a single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30, the fifth group received turmeric extract (100 mg·kg(-1)) orally for 30 days and a single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30, and the sixth group received turmeric extract (200 mg·kg(-1)) orally for 30 days and single dose of methotrexate (20 mg·kg(-1)) i.p. at day 30. Four days after methotrexate injection, animals were anesthetized, blood samples were taken to determine total antioxidant status (TAS) and jejunum samples were taken for glutathione peroxidase (GPx), superoxidase dismutase (SOD), catalase (CAT), aldehyde malondialdehyde (MDA), and histopathological assessment., Results: Microscopic evaluation from intestinal tissues of the MTX treated group, showed severe villus shortening and blunting, inflammatory cell infiltration and hemorrhage in lamina propria, along with epithlial cell necrosis. Levels of SOD, GSH-Px and CAT decreased in the MTX received group, but increased significantly (P < 0.05) in the turmeric + MTX groups. MTX increased lipid peroxidation, however, turmeric decreased peroxidation significantly (P < 0.05)., Conclusion: These results suggest that turmeric extract may protect the small intestine of rats from methotrexate-induced damage. Turmeric effects could result from its antioxidant properties., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objectives: This study was designed to determine the effects of zinc supplementation on oxidative stress in hemodialysis (HD) patients through evaluating total antioxidant capacity (TAC), whole blood glutathione peroxidase (GSH) level, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) level., Design and Setting: Double-blinded randomized controlled trialfrom October 2006 to December 2007 at Tabriz Imam Khomeini Hospital., Subjects: Sixty-five HD patients were randomly enrolled into 2 groups., Intervention: Patients received placebo in group A and zinc (100 mg/day) in group B for 2 months. After a washout period for 2 months, the groups were crossed over and the study was continued for an additional 2 months., Main Outcome Measures: Serum zinc concentration was measured using atomic absorption spectrophotometry. TAC, GSH level, and SOD activity were determined by commercial enzyme-linked immunosorbent assay kits. MDA level was measured using a thiobarbituric acid method., Results: The levels of serum zinc, TAC, GSH (P < .001 for all), and SOD activity (P < .001 for group A and P = .003 for group B) significantly increased after zinc supplementation whereas the serum level of MDA decreased after the same period (P = .003 for group A and P < .001 for group B)., Conclusions: Zinc supplementation for 2 months improved the serum levels of zinc, antioxidant status, and lipid peroxidation in HD patients., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background/aims: Gastric cancer, as the fourth most frequent malignancy worldwide, has the highest rate among cancer-related disorders in Ardabil province, located in North-West Iran. Methylene tetrahydrofolate reductase is one of the cancer susceptibility genes with considerable polymorphisms. Methylene tetrahydrofolate reductase C677T leads to a decrease of about 30% in its product activity and is reported to have an effect on cancer susceptibility., Materials and Methods: Methylene tetrahydrofolate reductase C677T genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism on peripheral blood DNA from 76 gastric cancer patients and 91 healthy controls. The statistical significance was calculated by logistic regression analysis., Results: The mean age was 64.2±11.1 and 62.1±9.8 years for cases and controls, respectively. Among tumors, 35.5% were diffuse type and others were intestinal. The frequency of genotypes was 61.8%, 32.9%, and 5.3% among cases and 45.1%, 50.6%, and 4.4% among controls for Ala/Ala, Ala/Val, and Val/Val, respectively. CT heterozygotes had lower susceptibility to gastric cancer (p=0.02). This relationship of significance was detected considering gender and age., Conclusions: It was found that T allele has a protective association with age in the Ardabil province.

Purpose: This study was conducted to assay cytotoxic effects of methylsulfonylmethane (MSM) on gastrointestinal cancer cell lines., Methods: Human gastric carcinoma (AGS), human hepatocellular carcinoma (HepG2), and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines were treated by MSM and incubated for 24, 48, and 72 h. Cytotoxicity was examined through MTT, neutral red uptake, and protein measurement assays. Ethidium bromide/acridine orange (EB/AO) staining was used for apoptotic cell detection. A diamidino-2-phenylindole staining method was used to analysis cell cycle by flow cytometry., Results: IC(50) of MSM on AGS, HepG2, and KYSE-30 cell lines were 28.04, 21.87 and 27.98 mg/ml after 72 h, respectively. The EB/AO staining showed an increase in apoptotic cells. Cell cycle analysis showed a significant increase in cell density at G2/M phase., Conclusion: MSM had cytotoxic effect on cancer cell lines but HepG2 cell line was more susceptible. This study suggests that MSM may induce cytotoxic effect on gastrointestinal cancer cell lines by apoptosis and cell cycle arrest.

Introduction: Pathogenic role of free radicals are well known in various metabolic diseases. They originate from internal and external sources of body. Essential roles of antioxidant defense system for cellular redox regulation and free radical scavenging activity were described in this study. Many in vitro investigations have shown that turmeric (TE) and carrot seed extract (CSE) exhibits to possess antioxidant activities. In this study, we evaluated the antioxidant potentials of ethanolic TE and CSE based on in vivo experiment in the rats., Methods: ANIMALS WERE ASSIGNED TO SIX GROUPS: the 1st and 2nd groups were control groups and 2nd group received 0.2 ml dimethyl sulphoxide as vehicle treated group; other four experimental groups received different doses of TE (100, 200 mg/kg b.w.) and CSE (200, 400 mg/kg b.w.) by gavages, respectively for a period of one month. The indicators of oxidative stress, lipids peroxidation, markers of hepatocyte injury and biliary function markers were measured., Results: The levels of superoxide dismutase, catalase, and glutathione peroxidase were significantly stimulated in the hepatic tissue of treatment groups. The malondialdehyde contents of liver tissue were significantly reduced in the groups fed with TE and CSE. Serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, in treated groups were found to be significantly decreased, whereas albumin and total protein increased as compared to the control groups (P<0.05)., Conclusion: this study showed that the regular intake of TE and CSE through the diet can improve antioxidant status and inhibit peroxidation activity in the liver tissue so that using these extracts may protect tissue oxidative stress.